18F-FDG PET uptake in the pre-Huntington disease caudate affects the time-to-onset independently of CAG expansion size
18F-FDG PET uptake in the pre-Huntington disease caudate affects the time-to-onset independently of CAG expansion size
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DOI：
10.1007/s00259-012-2114-z
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发表时间：
2012-06-01
影响因子：
9.1
通讯作者：
Squitieri, Ferdinando
中科院分区：
文献类型：
--
作者：
Ciarmiello, Andrea;Giovacchini, Giampiero;Squitieri, Ferdinando
为了在纵向随访研究中测试具有亨廷顿病 (HD) 遗传风险的受试者的基础葡萄糖代谢是否可能影响明显症状的发作。研究组由 43 名携带 HD 突变的症状前 (preHD) 受试者组成。他们接受了 F-18-FDG PET 扫描，并使用统一的 HD 评级量表进行了至少 5 年的前瞻性随访，以检测临床变化。多元回归分析将受试者的年龄、CAG 突变大小和葡萄糖摄入量作为预测发病年龄的模型中的变量。在 43 名表现出运动症状（提示 HD）的 HD 前期受试者中，PET 扫描 5 年后，26 名受试者的尾状核平均脑葡萄糖摄入量低于 1.0493 的截止值，显着低于 17 名保持无症状的 HD 前期受试者（P < 0.0001）。这种差异与突变大小无关。脑葡萄糖摄取的测量将用于预测发病年龄的 CAG 重复次数和基于年龄的模型提高了 37%。除了突变大小之外，大脑尾状核中葡萄糖代谢水平的降低可能是导致 HD 前期受试者 HD 发病年龄的一个诱发因素。
To test in a longitudinal follow-up study whether basal glucose metabolism in subjects with a genetic risk of Huntington disease (HD) may influence the onset of manifest symptoms.The study group comprised 43 presymptomatic (preHD) subjects carrying the HD mutation. They underwent a F-18-FDG PET scan and were prospectively followed-up for at least 5 years using the unified HD rating scale to detect clinical changes. Multiple regression analysis included subject's age, CAG mutation size and glucose uptake as variables in a model to predict age at onset.Of the 43 preHD subjects who manifested motor symptoms, suggestive of HD, after 5 years from the PET scan, 26 showed a mean brain glucose uptake below the cut-off of 1.0493 in the caudate, significantly lower than the 17 preHD subjects who remained symptom-free (P < 0.0001). This difference was independent of mutation size. Measurement of brain glucose uptake improved the CAG repeat number and age-based model for predicting age at onset by 37 %.A reduced level of glucose metabolism in the brain caudate may represent a predisposing factor that contributes to the age at onset of HD in preHD subjects, in addition to the mutation size.